| 11. |
- Rolstad, Sindre, 1976, et al.
(författare)
-
Amyloid-β₄₂ is associated with cognitive impairment in healthy elderly and subjective cognitive impairment.
- 2011
-
Ingår i: Journal of Alzheimers Disorder. - 1387-2877. ; 26:1, s. 135-142
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to predict cognitive performance on the basis of the cerebrospinal fluid (CSF) biomarkers total tau (T-tau) and amyloid-β42 (Aβ42) in controls and patients at various impairment levels. Previous studies have found an association of CSF T-tau levels with cognitive symptoms, but it has been difficult to relate Aβ to cognition, and it has thus been hypothesized that Aβ reaches a plateau level prior to cognitive symptoms. A comprehensive battery of neuropsychological tests was subjected to factor analysis to yield aggregated cognitive domains. Linear regression models were performed for the total sample of the Gothenburg MCI study (n = 435) and for each level of impairment. Aβ42 and T-tau accounted for a significant proportion of performance in all cognitive domains in the total sample. In controls (n = 60) and patients with subjective cognitive impairment (n = 105), Aβ42 predicted a significant proportion of semantic and working memory performance. For patients with mild cognitive impairment (n = 170), T-tau had the most pronounced impact across cognitive domains, and more specifically on episodic memory, visuospatial, and speed/executive performance. For patients with dementia (n = 100), the most pronounced impacts of Aβ42 were found in episodic memory and visuospatial functioning, while T-tau was substantially associated with episodic memory. Our results suggest that cognition is related to CSF biomarkers regardless of impairment level. Aβ42 is associated with cognitive functions from a potentially early to a later disease phase, and T-tau is more indicative of performance in a later disease phase.
|
|
| 12. |
- Rolstad, Sindre, 1976, et al.
(författare)
-
Cerebrospinal fluid biomarkers mirror rate of cognitive decline.
- 2013
-
Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 34:4, s. 949-56
-
Tidskriftsartikel (refereegranskat)abstract
- The ability to predict future decline in cognitive systems using the cerebrospinal fluid (CSF) biomarkers 42 amino acid form of amyloid-β (Aβ42) and total tau (T-tau) is not fully understood. In a clinical sample ranging from cognitively healthy to dementia (n = 326), linear regression models were performed in order to investigate the ability of CSF biomarkers to predict cognitive decline in all cognitive domains from baseline to 2-year follow-up. Gender, age, and years of education were included as covariates. In patients with subjective cognitive impairment, T-tau had a small impact on executive functions (r2 = 0.07). T-tau had a small to moderate influence (r2 = 0.06-0.11) on all cognitive functions with the exception of visuospatial functions in patients with mild cognitive impairment (MCI). In patients with dementia, the impact of T-tau was large (r2 = 0.29) on semantic memory. Aβ42 had a small effect (r2 = 0.07) on speed and executive functions in MCI. In patients with dementia, Aβ42 had a moderate influence (r2 = 0.13-0.24) on semantic and verbal working memory/fluency. Our results speak in favor of the notion that CSF biomarkers reflect the rate of cognitive decline across the continuum of cognitive impairment from healthy to dementia. CSF predicted subsequent decline in more cognitive domains among MCI cases, but the impact was most pronounced in patients with dementia.
|
|
| 13. |
- Rolstad, Sindre, 1976, et al.
(författare)
-
High Education May Offer Protection Against Tauopathy in Patients with Mild Cognitive Impairment.
- 2010
-
Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 21:1, s. 221-8
-
Tidskriftsartikel (refereegranskat)abstract
- The concepts of brain and cognitive reserve stem from the observation that premorbid factors (e.g., education) result in variation in the response to brain pathology. Potential early influence of reserve on pathology, as assessed using the cerebrospinal fluid biomarkers total tau and amyloid-beta{42}, and cognition was explored in mild cognitive impairment (MCI) patients who remained stable over a two-year period. A total of 102 patients with stable MCI grouped on the basis of educational level were compared with regard to biomarker concentrations and cognitive performance. Stable MCI patients with higher education had lower concentrations of t-tau as compared to those with lower education. Also, educational level predicted a significant proportion of the total variance in t-tau concentrations. Our results suggest that higher education may offer protection against tauopathy.
|
|
| 14. |
- Rolstad, Sindre, 1976
(författare)
-
The reserve concept in patients with Mild Cognitive Impairment – new approaches
- 2010
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The concept of reserve stems from the observation that premorbid factors, e.g. education, result in variation in the response to any kind of brain pathology. As subjects with higher reserve tolerate more neuropathology, symptomatic expression of pathology is delayed. It is thus predicted that neuropathology should be more pronounced in those with higher reserve as compared to those with lower at the same level of clinical severity. Most research within the reserve paradigm has been conducted on patients with established diagnoses, mainly Alzheimer’s disease, but knowledge on the modifying effects of reserve in preclinical, Mild Cognitive Impairment (MCI), and early phases of dementia is limited. The main purpose was to investigate if use of cerebrospinal fluid (CSF) biomarkers, would enable studies of reserve in earlier phases. Specifically, the 42 amino acid form of beta-amyloid (abeta42), mirroring amyloid plaques depositions, and CSF total tau (t-tau), reflecting axonal degeneration, were used as surrogate measures for neuropathology. Another purpose was to explore if patients with higher reserve diverge from patients with intermediate and lower reserve in terms of CSF pathology, and cognitive functioning in various disease phases. As premorbid intelligence Quotient (IQ), cognitive functioning prior to manifest disease, may be a better proxy for reserve than education, the final objective was to construct a test for assessment of premorbid IQ in Swedish. In summary, we found that patients with higher reserve were distinguishable from those with intermediate and lower reserve with regards to abeta42 pathology, but not clinical manifestations. The incongruence between pathology and clinical outcome indicates compensation for neuropathology. We also found that abeta42 may be sensitive to disease progress when taking level of reserve into account. Patients with higher reserve with stable MCI had lower concentrations of CSF t-tau, but comparable abeta42 concentrations. This finding may either indicate a true protective effect for education, or suggests that higher education promotes cognitive stimulation resulting in better axonal integrity. Also, a test for assessment of premorbid IQ, NART-SWE, was successfully constructed and found to have satisfactory psychometric properties. The results of these studies may contribute to earlier identification, and consequentially treatment of patients with higher reserve at risk for dementia.
|
|
| 15. |
- Wallin, Anders, 1950, et al.
(författare)
-
Progression from mild to pronounced MCI is not associated with cerebrospinal fluid biomarker deviations.
- 2011
-
Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 32:3, s. 193-7
-
Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: Detection of cerebrospinal fluid (CSF) biomarker deviations improve prediction of progression from mild cognitive impairment (MCI) to dementia. However, it is not settled whether the same pattern exists in patients progressing from very mild to more pronounced MCI. Given that neurodegenerative processes occur very early in the disease course, we also expected to find biomarker deviations in these patients. Methods: A total of 246 memory clinic patients with non-progressive (n = 161), progressive (n = 19), or converting (n = 66) MCI, 67 with stable dementia, and 80 controls were followed for 24 months. At baseline, CSF total tau (T-tau), β-amyloid 1–42 (Aβ42) and the light subunit of neurofilament protein (NFL) were determined. Results: Patients with converting MCI and stable dementia had lower CSF Aβ42 concentrations and higher T-tau concentrations and NFL in comparison with controls and non-progressive/progressive MCI (p < 0.0005). No differences were found between progressive and non-progressive MCI. Conclusion: As expected, biomarker deviations predicted progression from MCI to dementia. Contrary to our hypothesis, progression from very mild MCI to more pronounced MCI was not reflected by biomarker deviations. The results suggest that the measured biomarkers are not early disease markers, or alternatively Alzheimer or vascular pathology is not the underlying cause in this patient group.
|
|
| 16. |
- Åstrand, Ragnar, et al.
(författare)
-
Cognitive Impairment Questionnaire (CIMP-QUEST): reported topographic symptoms in MCI and dementia.
- 2010
-
Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 121:6, s. 384-391
-
Tidskriftsartikel (refereegranskat)abstract
- Astrand R, Rolstad S, Wallin A. Cognitive Impairment Questionnaire (CIMP-QUEST): reported topographic symptoms in MCI and dementia. Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2007.01312.x. (c) 2009 The Authors Journal compilation (c) 2009 Blackwell Munksgaard. Objective - The Cognitive Impairment Questionnaire (CIMP-QUEST) is an instrument based on information obtained by key informants to identify symptoms of dementia and dementia-like disorders. The questionnaire consists of three subscales reflecting impairment in parietal-temporal (PT), frontal (F) and subcortical (SC) brain regions. The questionnaire includes a memory scale and lists non-cognitive symptoms. The reliability and validity of the questionnaire were examined in 131 patients with mild cognitive impairment (MCI) or mild dementia at a university-based memory unit. Methods/Results - Cronbach alpha for all subscales was calculated at r = 0.90. Factor analysis supported the tri-dimensionality of CIMP-QUEST's brain region-oriented construct. Test-retest reliability for a subgroup of cognitively stable MCI-patients (n = 25) was found to be r = 0.83 (P = 0.0005). The correlation between the score on the cognitive subscales (PT + F + M) and Informant Questionnaire on Cognitive Decline in the Elderly was r = 0.83 (P = 0.0005, n = 123). The memory subscale correlated significantly with episodic memory tests, the PT subscale with visuospatial and language-oriented tests, and the SC and F subscales with tests of attention, psychomotor tempo and executive function. Conclusions - CIMP-QUEST has high reliability and validity, and provides information about cognitive impairment and brain region-oriented symptomatology in patients with MCI and mild dementia.
|
|
